A NOVEL AMINO-ACID MODIFICATION IN SULFATASES THAT IS DEFECTIVE IN MULTIPLE SULFATASE DEFICIENCY

Multiple sulfatase deficiency (MSD) is a lysosomal storage disorder ch aracterized by a decreased activity of all known sulfatases. The defic iency of sulfatases was proposed to result from the lack of a co- or p osttranslational modification that is common to all sulfatases and req uired for their catalytic activity. Structural analysis of two catalyt ically active sulfatases revealed that a cysteine residue that is pred icted from the cDNA sequence and conserved among ail known sulfatases is replaced by a 2-amino-3-oxopropionic acid residue, while in sulfata ses derived from MSD cells, this cysteine residue is retained. It is p roposed that the co- or posttranslational conversion of a cysteine to 5-amino-3-oxopropionic acid is required for generating catalytically a ctive sulfatases and that deficiency of this protein modification is t he cause of MSD.